The project is a collaboration between the Bill and Melinda Gates Foundation, with investigators from Stellenbosch University (SUN) and the University of Cape Town (UCT). One trial is ongoing, initiated in FY2016. NIAID 15-I-N070: NexGen EBA radiologic and immunologic biomarkers to enhance early bactericidal activity measurements of sterilizing drug activity in tuberculosis. This study begain in FY2016 with the hypothesis that drug regimens associated with higher sterilizing activity (e.g., containing rifampin or pyrazinamide) will show distinctive early cytokine and chemokine patterns and discrete, quantifiable changes on PET/CT in certain lesion types during the 2-week early bactericidal activity (EBA) treatment period, compared to drug regimens with poor sterilizing activity (e.g., containing isoniazid or moxifloxacin). Demonstration of such an association would provide rationale for including radiologic and immunologic analysis, alongside conventional EBA, in early phase clinical studies of novel drugs, and would also provide important new insights into the biology of human and bacterial responses to TB drugs. The primary objective is to characterize, in the context of a standard EBA study, the effect of various antituberculosis drugs on radiographic and immunologic markers as measured by PET/CT and immunologic assays, in treatment-nave subjects with pulmonary drug sensitive tuberculosis. If adding immunologic and/or radiographic markers to the standard EBA microbiologic markers improves the ability of EBA studies to predict sterilizing treatment, the EBA studies may be able to predict better which novel drugs or drug combinations will be more effective and thereby should move forward into phase 2 or 3 trials. The study initiated on December 3, 2015 and, as of August 11, 2016, has screened 107 subjects and enrolled 69 subjects.